PL142760B1 - Process for preparing novel derivatives of piperazine - Google Patents

Abstract

Novel compounds of the general formula (I) and the pharmaceutically acceptable esters and acid addition salts thereof, wherein: R1, R2, R3, R4 and R5 are each independently hydrogen, lower alkyl, lower alkoxy, cyano, trifluoromethyl, halo, lower alkylthio, lower alkyl sulfinyl, lower alkyl sulfonyl, N-optionally substituted alkylamido, except that when R1 is methyl, R4 is not methyl; or R2 and R3 together form -OCH2O-; R6, R7, R8, R9 and R10 are each independently hydrogen, lower acyl, aminocarbonylmethyl, cyano, lower alkyl, lower alkoxy, trifluoromethyl, halo, lower alkylthio, lower alkyl sulfinyl, lower alkyl sulfonyl, di-lower alkyl amino; or R6 and R7 together form -CH=CH-CH=CH-; R7 and R8 together form -OCH2O-; R11 and R12 are each independently hydrogen or lower alkyl; and W is oxygen or sulfur. These cardioselective compounds have calcium entry blockade properties and therefore are useful in therapy in the treatment of cardiovascular diseases, including arrhythmias, variant and exercise induced angina and myocardial infarction.

Description

***** l«*-V "tr lt«*lj Int. Cl4 C07D 295/08 C07D 295/10 Inventors: Arthur Frederick Kluge, Robin Douglas Clark, Arthur Martin Strosberg, Jean Claude Pascal, Roger Lewis Whiting Patent holder: Syntex (USA) Inc., Palo Alto, California (United States of America) Method for preparing new piperazine derivatives The subject of the invention is a method for preparing new piperazine derivatives, useful in the treatment of human diseases affected by blocking calcium entry. These new derivatives are compounds in which the piperazine group is bonded via one nitrogen atom to an aryloxy or arylthio group via a hydroxypropylene or alkanoyloxypropylene bridge, and via the second nitrogen atom to a acetanilide. Many compounds are known that act on various adrenergically controlled physiological systems. Compounds related to the compounds prepared by the process of the invention are disclosed in Belgian Patent No. 806,380 (U.S. Patent No. 3,944,549) and include 1-(1,4-benzodioxinal-2-methyl)-4-(2,6-dimethylphenylacetanilido)piperazine, in the publication by W. Stankeviciene et al., Mater. Mezhvug. Nauchv. Koni. Kaunos. Med. Inst. 25 (1976), published in 1977, pp. 322-323 [Chem. Abstr. 90, 54907 c (1979)] and in French Patent No. 2,267,104. Additional publications related to this field include U.S. Patent Nos. 4,360,529, 3,496,183, 3,829,441, 3,879,401, 3,944,549, 4,059,621, 4,302,459, 4,315,939, 4,335,126 and 4,353,901. Calcium entry blocking compounds are used to influence the symptoms of cardiovascular diseases such as myocardial infarction, right ventricular failure, angina and arrhythmia. The compounds produced by the method According to the invention, they are cardioselective drugs and are useful in the treatment of these diseases of the cardiovascular system. By the method according to the invention, compounds of the general formula 1 are prepared, wherein R1, Rf, R1, R4 and R5 are the same or different and represent a hydrogen atom, a lower alkyl group, a lower alkoxy group, a cyano group, a trifluoromethyl group, a halogen atom, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkylsulfonyl group, an alkylamido group optionally substituted on the nitrogen atom, or R* and R3 together form a —OCH1O— group, R6, R7, R8, R* and R10 are the same or different and represent a hydrogen atom, a lower acyl group, a aminocarbonylmethyl, cyano group, lower alkyl group, lower alkoxy group, trifluoromethyl group, halogen atom, lower alkylthio group, lower alkylsulfinyl group, lower alkylsulfinyl group, lower dialkylamino group, * or R6 and R7 together form the group —CH=CH—CH=CH— or R7 and R8 together form the group —OCH2O—, R11 and R12 are the same or different and represent a hydrogen atom or a lower alkyl group, and W represents an oxygen or sulfur atom, and when R1 represents a methyl group, then R4 has a meaning other than a methyl group, and pharmacologically acceptable esters and acid addition salts of these compounds. 142 760142 760 3 Compounds These drugs are cardioselective and are therapeutically useful in the treatment of cardiovascular diseases, including arrhythmia, angina induced by altered conditions or exertion, and myocardial infarction. The term "aminocarbonylmethyl" refers to a group of the formula —CH1—C(=O)—NH*. The term "aryl" refers to an optionally substituted phenyl or naphthyl group in which R6 and R7 together form a group —CH=CH—CH=CH. The term "cyano" refers to a group of the formula —C=N. The term "dialkyl lower amino" refers to a group of the formula R13 (R14)N—, wherein R14 and R14 are the same or different lower alkyl radicals with the meaning given below. The term "atom" refers to a group of the formula R13 (R14)N—, wherein R13 and R14 are the same or different lower alkyl radicals with the meaning given below. "halogen" refers to a fluorine, chlorine, bromine, or iodine atom, which is usually a halogen substituent replacing a hydrogen atom in organic compounds. The term "isomer" refers to compounds having the same atomic mass and atomic number but differing with respect to one or more physical or chemical properties. The different types of isomers are discussed below. The term "stereoisomer" refers to a chemical compound having the same molecular mass, chemical composition, and structure as another compound, but with the atoms arranged differently. Thus, certain identical chemical moieties have a different orientation in space and therefore, in pure form, exhibit the ability to rotate the plane of plane-polarized light. However, for some pure stereoisomers, the optical rotation may be so slight that it is undetectable using currently available equipment. The term "optical isomerism" describes a type of stereoisomerism that characterizes the rotation that an isomer, pure or in solution, exerts on plane-polarized light. In many cases, this is due to the attachment of four different atoms or chemical groups to at least one carbon atom in the molecule. Such isomers may be designated as d-, l- or a d, l-pair, or as D-, L- or a D, L-pair, or as R-, S- or an R, S-pair, depending on the nomenclature system adopted. The term "diastereomer" refers to stereoisomers (some or all of which are unsymmetrical but are not mirror images of each other). Diastereomers corresponding to a given structural formula must contain at least two asymmetric atoms. A compound with two asymmetric atoms usually exists as four diastereomers, i.e. (—)-erythro, (+)-erythro, (—)-thoreo and (+Mreo). Some compounds of formula I, in which R1S is hydrogen, contain one asymmetric carbon atom, i.e. the carbon atom at position 2 of the moiety. These compounds exist in the form of two stereoisomers, i.e. (+) and (—), i.e. R and S, and mixtures thereof. Compounds of formula I, in which R11 is a group other than hydrogen, contain two asymmetric carbon atoms, i.e. the carbon atom in position 2 of the propyl moiety and the carbon atom to which the R11 substituent is bonded. These compounds exist in the form of four stereoisomers, i.e. (+)-erythro, (—)-erythro, (+)-threo, (—Mreo), and mixtures thereof. In accordance with the Cahn-Prelog convention, these four isomers are designated R—R, R—S, S—R, and S—S, which describe the stereoisomerism of each of the asymmetric carbon atoms. In this description, the designations σ and S are used. The scope of the invention includes the individual stereoisomers as well as mixtures thereof. The term "structure of formula I" refers to the basic structure of the compounds prepared by the process of the invention. The chemical bonds marked with a wavy line in formula I denote non-specific stereoisomerism of asymmetric carbon atoms, e.g., in position 2 of the propyl chain, i.e., the carbon atom to which the hydroxyl group (-OH) is attached, and also the carbon atom to which the R1* substituent is attached, between the piperazine ring and the carbonyl group. The term "lower acyl group" refers to a group of formula R15-<O=)C-, wherein R15 is a lower alkyl radical as defined below, and includes groups such as acetyl, propionyl, n-butyryl, and the like. The term "lower acyl group" refers to a group of formula R15-<O=)C-, wherein R15 is a lower alkyl radical as defined below, and includes groups such as acetyl, propionyl, n-butyryl, and the like. "alkyl" or "lower alkyl" means a branched or unbranched saturated hydrocarbon chain such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl and tert-butyl. The term "lower alkoxy" refers to a group of the formula —OR, wherein R is a lower alkyl radical as defined above. The term "lower alkylthio" refers to a group of the formula —SR, wherein R is a lower alkyl radical as defined above. The term "lower alkylsulfinyl" refers to a group of the formula —S(=O)—R, wherein R is a lower alkyl radical as defined above. The term "lower alkylsulfonyl" refers to a group of the formula -h(O=)S(=O)-R, wherein R50 is a lower alkyl radical as defined above. The term "alkylamide group optionally substituted on nitrogen" refers to a group of the formula -N(R16)-O(=O)-R17, wherein R15 is hydrogen or a lower alkyl radical and R17 is a lower alkyl radical as defined above. The term "optionally" means that the subsequently described fact or condition may or may not hold, so that the description of that fact or condition includes the instances of its occurrence or non-occurrence. For example, the term "phenyl group optionally substituted" means that the phenyl group may or may not be substituted. The term "where the free base is optionally converted to an acid addition salt" means that in the process of the invention this conversion may or may not be carried out, so that processes in which the free base is converted to an acid addition salt and processes in which the base is not converted to a salt are included within the scope of the invention. The term "pharmaceutically acceptable acid addition salt" refers to salts which retain the biological activity and properties of the free bases and which are not biologically or otherwise undesirable. Such salts are salts of inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc., or organic acids such as acetic acid, propionic acid, hydrocollic, pyruvic, oxalic, malic, malonic, succinic, maleic, fumaric, tartaric, citric, benzoic, cinnamic, mandelic, methanesulfonic, ethamosulfonic, p-toluenesulfonic, salicylic, etc. The term "pharmacologically acceptable ester" refers to an ester of a compound of formula I which can be conveniently used in therapy and includes compounds containing an alkanoyloxy group of the formula —O—Ofl=O)—Z, wherein Z is an alkyl radical of 1 to 12 carbon atoms, attached to the carbon atom in position 2 of the propylene chain instead of the hydroxyl group, i.e. the hydroxyl group has been esterified. The substituent Z may be, for example, a methyl radical, ethyl, butyl, hexyl, octyl, dodecyl, etc. The scope of the invention includes compounds of formula 1 which are the above-described esters and at the same time are pharmacologically acceptable salts of these compounds with acids. The piperazine moiety is a saturated, six-membered, two-nitrogen-containing, substituted heterocyclic moiety of formula 2. The compounds prepared by the method according to the invention are generally named according to the IUPAC nomenclature system. The position of substituents in the ring system in these compounds is given in formula 1. For example, when R1 and R5 are methyl groups, R8 is a methoxy group, R1-R4 and R7-R1f are hydrogen atoms, and W is an oxygen atom, then This compound is named 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine and is defined by formula 3, where the asterisk denotes a center or a possible asymmetric center. This compound may also be named 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylcarbamoylmethyl)piperazine or 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylacetanilido)piperazine. The IUPAC nomenclature will be used in this description. Optically active compounds can be named according to a number of conventions, i.e., according to the priority rules. Cahn and Prelog by the symbols R and S, as arythrom and threo isomers, as D and L isomers, as diisomers, and as isomeric (+) and (—), which indicate the direction in which the plane of polarized light is rotated by the chemical compound, either pure or in solution. These conventions are well known and are described in detail by E. L. Eliel in Stereochemistry of Carbon Compounds, McGraw Hill Book Company Inc., New York, 1962. Preferred compounds of the invention are those of formula I wherein two of the substituents R*-^R* are hydrogen atoms and two of the substituents R8-^R11 are hydrogen atoms. A preferred subgroup are those of formula I wherein W is oxygen. A preferred subgroup includes those compounds of formula I in which the substituents R5, R6 and R7 are hydrogen atoms. Another preferred subgroup includes those compounds of formula I in which the two substituents R1 and R1 are lower alkyl groups, especially methyl. Particularly preferred compounds of the invention are: a compound of formula I in which the substituents R1 and R5 are methyl groups, Rf, R*, R4 and R11 are hydrogen atoms and W is an oxygen atom, i.e. 1-[3-phenoxy-2-hydroxypropyl]-(2,6-dimethylphenylaminocarbonylmethyl)piperazine, a compound of formula I in which R1 and R5 are methyl, R* is a methoxy group, R1, R3, R4 and R7-R1* are hydrogen atoms and W is an oxygen atom, i.e. 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine, and a compound of formula I, in which R1 and R5 are methyl groups, R6 is a cyano group, Rf, R*, R4 and R7-R11 are hydrogen atoms and W is an oxygen atom, i.e. 1-[3-(2-cyanophenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine. Also preferred are compounds of formula I in which the two substituents R* and R* are different than hydrogen atoms and denote halogen atoms, especially chlorine. Also preferred are compounds of formula I in which at most one of the substituents R1-R2 is other than a hydrogen atom. A particularly preferred subgroup is formed by compounds in which this other substituent is R1, and another preferred subgroup is formed by compounds in which this one other substituent is a lower alkoxy group, especially methoxy. Also preferred are compounds of formula I in which two of the substituents R7-R9 are other than a hydrogen atom, and a particularly preferred subgroup is formed by compounds in which R6 and R1f are lower alkoxy groups, especially methoxy. Also preferred are compounds of formula I in which at most one of the substituents is R6 - Rw is other than a hydrogen atom. Among these, a preferred subgroup is formed by compounds in which the substituent R6 is a lower alkoxy group, especially methoxy, and another preferred subgroup is formed by compounds in which R*142 760 T is a cyano group or a halogen atom, especially chlorine. A preferred subgroup is also formed by compounds of formula I, in which the substituent R8 is other than a hydrogen atom and is a lower alkoxy group, especially methoxy, or a chlorine atom. Furthermore, preferred are compounds of formula I in which R11 is a hydrogen atom, compounds of formula I in which R12 is a hydrogen atom, and also compounds of formula I in which R11 and R12 are The process according to the invention also produces compounds of formula I, wherein W is a sulfur atom. Preferred subgroups include compounds in which R12 is a lower alkyl group, especially methyl, and compounds in which R11 and R12 are lower alkyl groups, especially methyl. Particularly preferred sulfur-containing compounds are 1-[3-(phenylthio)-2-hydroxypropyl]-N-methyl-N-phenylaminocarbonyl-1-ethyl)piperazine and 1-(3-phenylthio-2-hydroxypropyl)-4-N-methyl-N-phenylaminocarbonyl-1-ethyl)piperazine. Preferred are compounds of formula I, in which R6, R7, R8, R9 and R11 are hydrogen atoms, and in particular those compounds in which R1-R10 are hydrogen atoms." Another preferred group of compounds includes those compounds in which R11 is hydrogen. Of this group, particularly preferred are compounds in which R1-R1 represents hydrogen. Among these compounds in which R1 represents hydrogen, the following compounds are particularly preferred: 1-[3-(2-methoxyphenoxy)-2-hydroxypyrro-pyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(4-chlorophenylaminocarbonylmethyl)piperazine, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(4-chlorophenylaminocarbonylmethyl)piperazine, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(4-chlorophenylaminocarbonylmethyl)piperazine, 1-[3-(2-methylphenylaminocarbonylmethyl)piperazine, 1-[3-(2-methylphenoxy)-2-hydroxypropyl]-4-(4-methoxyphenylaminocarbonylmethyl)piperazine, 1-[3-(2-methylphenoxy)-2-hydroxypropyl]-4-(4-methylphenylaminocarbanylmethyl)piperazine, 1-[3-(2-methylphenylaminocarbonylmethyl)piperazine, 1-[3-(2-methylphenylaminocarbanylmethyl)piperazine, 1-[3-(2-methyloxyphenyl)-2-hydroxypropyl]-4-(2,6-dimethylphenylamino)piperazine and 1-B'(1-(2-methyloxyphenyl)-2-hydroxypropyl)-4-(2,6-dimethylphenylaminocarboxymethyl)piperazine. Furthermore, compounds in which R11 and R12 represent methyl groups are preferred, especially 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-(2,6-dimethylphenyl)-N-methylamino)piperazine. The compounds produced by the process of the invention are used for the production of pharmacological agents useful in the treatment of one or more diseases of the respiratory system. The invention also provides a method for treating cardiovascular disorders, such as arrhythmia, myocardial infarction, and angina induced by altered conditions or exertion, in mammals, and especially humans. The invention provides a therapeutically effective amount of a compound of formula I or a pharmacologically acceptable acid addition salt thereof in admixture with a pharmacologically acceptable excipient. The treatment of the aforementioned diseases comprises administering to a patient in need of treatment a therapeutically effective amount of a compound of formula I or a pharmacologically acceptable acid addition salt thereof. The preferred compounds described above include the (+) and (—) optical isomers and the R and S isomers, as well as mixtures thereof. The invention encompasses the individual isomers and all possible mixtures thereof. All process variants for the preparation of the above-mentioned compounds are hereinafter referred to as the invention. include the preparation of pharmacologically acceptable esters and acid addition salts of these compounds, especially mono- and dihydrochlorides, and mixtures thereof. A process for the preparation of compounds of formula I and their pharmacologically acceptable esters and acid addition salts, according to the invention, comprises reacting a compound of general formula IV, wherein R6, R7, R8, R9, R10 and W have the meanings given above, with a compound of general formula V, wherein X is a leaving group and R1, R2, R13, R4, R5, R11 and R12 have the meanings given above, or converting the compound of formula I in salt form into the free base, or converting the compound of formula I in free base form into a pharmacologically acceptable acid addition salt, or a salt of the compound of formula 1 is converted into another pharmacologically acceptable salt of the compound of formula 1, or the compound of formula 1 or a salt thereof is converted into a pharmacologically acceptable ester, or the compound of formula 1 or a salt or ester thereof is separated into stereoisomers. The method of linking two parts of the compound of formula 1 via the piperazine ring is illustrated in the diagram in which Ar1, Ar2 and X have the meanings given below. The symbol "Ar1" denotes an optionally substituted aryl group of formula 6, in which the substituents R6-R11 have the meanings given above. The connection with other parts of the molecule takes place via the carbon atom in position 1, i.e. to the oxygen or sulfur atom. The positions of the aryl group are numbered as given. The symbol "Ar2" denotes an optionally substituted aryl group. The phenyl group of formula 7, wherein the substituents R 1 -R 5 have the meanings given above, and the positions are numbered as given. The symbol X denotes a leaving group, such as, for example, a halogen atom or a sulfur ester group, preferably a halogen atom. The starting compounds used in the reactions shown are obtained as described below. The compound of formula 10, wherein Ar 1 has the meaning given above, is obtained by reacting the appropriate phenol with 2,3-isopropylidynyl-1-tosylpropane, hydrolyzing it with an aqueous acid solution, followed by reaction with methanesulfonyl chloride or toxenesulfonyl chloride and pyridine and further reaction with sodium hydroxide. This method is well known in the art. from Caroon et al. J. Med. Chem. 24, 1320 <1981). Aryloxy- and arylthio-epoxy compounds of formula 10 can also be prepared by reacting an unsubstituted or substituted phenol or thiophenol of formula 8 with epichloridrine of formula 9 in the presence of a strong base, such as Triton S, trialkylamines, alkali metal hydroxides, alcoholates or hydrides, e.g. sodium or potassium hydroxide, methanolate or hydride. The reaction is carried out in an inert solvent, such as methanol, ethanol, dimethylformamide, dimethylsulfoxide, etc., at room temperature for about 20 hours. This method is described, for example, in G. Shtacher et al., J. Med. Chem. vol. 16, no. 5, p. 516ff <1973). Phenols and phenols are readily available, and if not readily available, they can be prepared by known methods. For example, numerous substituted phenols are commercially available. These include methyl-, dimethyl-, trimethyl-, ethyl-, diethyl-, propyl-, butyl-, methoxy-, dimethoxy-, trimethoxy-, ethoxy-, diethoxy-, propoxy-, butofcsy-, cyano-, chlorine-, dichloro-, trichloro-, tetrachloro-, pdeciochloro-, bromo-, dibromo-, tri-TDromo-, fluoro-, difluoro-, trifluoro-, bromo-chloro-, bromofluoro-, chlorofluoro-, methylthio, methylenedioxyphenols and mixtures of the foregoing compounds as described in "Chemical Sources", Directories Publishing-Company, Inc., Flemington, New Jersey, 1979. Phenols substituted methylsulfinyl or methylsulfonyl group is prepared according to known methods starting from methylthiophenol, which is commercially available or can be readily prepared. For example, o-methylsulfinylphenol is prepared by treating o-methylthiophenol with acetic anhydride to form the corresponding ester, which is treated with sodium periodate from methanol. After hydrolysis under acidic or basic conditions to remove the acetyl group, o-methylsulfinylphenol is obtained. O-Methylsulfonylphenol is prepared by treating the above-mentioned ester with hydrogen peroxide or 2-chloroperoxybenzoic acid in aqueous methanol. After hydrolysis to remove the acetyl group, o-methyl-, sulfonylphenol is obtained in good yield. The corresponding m- and p-methylsulfinylphenols and methylsulfonylphenols are similarly prepared by replacing o-methylthiophenol with n-methyl and p-methylthiophenol, respectively. According to the scheme, compounds of formula 10 can be converted to compounds of formula 14 by reacting the resulting phenoxy-substituted epoxide derivatives with a piperazine of formula 11 by heating in a solvent that dissolves both reactants, according to known methods, e.g., the method of Carson et al. (see reference cited above). Compounds of formula 15 are prepared from the appropriate aniline, substituted aniline, or N-substituted aniline derivatives of formula 13, which are commercially available, by reaction with halides. α-haloacyls such as α-monochloroacetyl chloride or α-chloropropionyl chloride, i.e. compounds of formula 12. Numerous substituted anilines are commercially available. These include methyl-, dimethyl-, trimethyl-, ethyl-, diethyl-, propyl-, butyio-, methoxy-, dimethoxy-, trimethoxy-, ethoxy-, dimethoxy-, propoxy-, butoxy-, chloro-, dichloro-, trichloro-, tetrachloro-, pentachloro-, bromo-, dibromo-, tribromo-, fluoro-, difluoro-, trifluoro-, bromochloro, bromofluoro-, fluorofluoro-, methylthio-, methylenedioxy-, anilines and mixtures of the above-mentioned compounds. Numerous N-alkyl derivatives of aniline such as N-methyl-, N-ethyl-, N-propyl-, and N-butyl-anilines and substituted anilines are also commercially available as reported in "Chemical Sources", Directories, POblishing Company, inc., Flemington, New Jersey, 1979. Anilines substituted with a methylsulfinyl or methylsulfonyl group are prepared according to known methods starting from the corresponding commercially available methylthioaniline. For example, o-methylsulfinylamine is prepared by treating o-methylthioaniline with acetic anhydride to form the corresponding acetanilide, which is treated with sodium periodate in methanol. After hydrolysis under acidic or basic conditions to remove the acetyl group, o-methylsulfonylaniline is obtained. o-Methylsulfonylaniline is obtained by treating the above-mentioned acetanilide with hydrogen peroxide or 2-chloroperoxybenzoic acid in aqueous methanol. After hydrolysis to remove the acetyl group, o-methylsulfonylaniline is obtained in good yield. The corresponding m- and p-methylsulphinylanils and methylsulphinylanilines are similarly prepared by replacing o-methylthioaniline with m-methyl and p-methylthioaniline, respectively. The corresponding ethyl, propyl, and butylthioanilines are obtained by treating commercially available amoxythiophenol with sodium hydroxide and then treating the resulting compound with the appropriate alkyl iodide. The corresponding ethyl-, propyl-, and butyl-sulphonyl- and sulphonyl-anilines are prepared by replacing o-methylthioaniline with the appropriate alkylthioaniline in the reactions described above. Numerous N-alkyl-substituted anilines can be prepared by known methods, e.g., by treating substituted or unsubstituted aryl-substituted anilines described herein with an alkyl halide such as methyl chloride, ethyl chloride, propyl chloride, butyl chloride, and the like, in a suitable solvent such as diethyl ether or dichloromethane. Numerous α-halo acid halides are commercially available, e.g., chloroacetyl chloride and α-chloropropionyl chloride. α-Chlorobutyric acid is commercially available and can be converted to the acid chloride by known methods, e.g., by reaction with thionyl chloride or phosphorus pentachloride. α-Chloroacid chlorides, which are not readily available, can be prepared by known methods, e.g., by the Hell-Volhard-Zelinsky reaction, which involves treating the appropriate alkanoic acid with chlorine in the presence of phosphorus. This method is given, for example, in R.T. Morrison and R.N. Boyd, "Organic Chemistry," 2nd ed., Chapter 18, p. 604, and in Chem. Revs., Vol. 7, p. 180 (1930). To carry out the reaction, the product of which is the compound of formula (XV), the aniline derivative, a basic amine such as triethylamine or pyridine, preferably triethylamine, and chloroacetyl chloride are dissolved in an inert aprotic organic solvent such as, for example, benzene, chloroform, carbon tetrachloride, methylene or methylene chloride, preferably methylene chloride. The aniline and the tertiary amine are used in approximately equimolar amounts, and the acetyl chloride is added in a slight molar excess, i.e., about 1.2-2 molar excess, preferably 1.3-1.5 molar excess, relative to the aniline. The mixture is cooled to about -10°C to +30°C, preferably in an ice bath, before the acyl halide is added. The mixture is kept at this low temperature for about 0.5 to 8 hours, preferably 4 hours, with stirring. The resulting compound of formula 15 is isolated by known methods. Compounds of formula 16, wherein Ar 1 , Ar 2 , R 1 -R 1 6 and W are as defined above, i.e. compounds of formula 1, are prepared by reacting a compound of formula 14 with a compound of formula 15 in the presence of a solvent such as a mixture of toluene and methanol, ethanol and dimethylformamide, etc. The reaction mixture is heated at a temperature of about 60°-150°C, preferably about 70°-90°C, for about 6-20 hours. Isolation and purification of the compounds described herein, including intermediates, can, if necessary, be carried out by any suitable methods, such as, for example, filtration, extraction, crystallization, column chromatography, etc. Thin-layer chromatography and thick-layer chromatography, as well as combinations of these methods. Specific examples of the isolation and purification techniques used are given in the Example, and any other appropriate methods can be used. Salt products are also isolated by known methods. For example, the reaction mixture may be evaporated to dryness and the salts further purified by known methods. Compounds of formula I prepared by the reactions described herein may exist in the form of R and S isomers (i.e., arythro and threo isomers). Thus, by the process of the invention, these compounds may be prepared as R or S isomers or mixtures thereof. Unless otherwise stated, the compounds prepared are mixtures of the R and S forms. However, the scope of the invention is not limited to R/S mixtures and also includes individual isomers of the compounds of formula I. If desired, the mixture of intermediates used in the preparation of the compounds of formula I as end products of the process can be separated, for example, by recrystallization and chromatography. Individual isomers of the compounds of formula I are preferably prepared from isomeric intermediates. The compounds of formula I described herein may exist as mixtures of optical isomers because of the possible existence of two asymmetric carbon atoms. Thus, they may be prepared in optically active form or as racemic mixtures. Unless otherwise stated, all compounds described herein are in racemic form. However, the scope of the invention is not limited to mixtures of racemic forms and also includes any individual optical isomers. If desired, racemic intermediates of formulae 8, 10, 12, 14 or 15 or the racemic product of formula 16 may be resolved into their optical antipodes by known methods, such as separation (e.g., by fractional crystallization) of diatereomeric salts formed by reaction of, for example, racemic compounds of formula 16 or intermediates of formulae 8, 10, 12, 14 or 15 with an optically active acid. Examples of such optically active acids are the optically active forms of camphor-10-sulfonic acid, α-bromocamphor-3-sulfonic acid, camphoric acid, malic acid, diacetyltartaric acid, pyrrolidone-5-carboxylic acids, etc., and examples of optionally used bases are cinchonidine, bucine, etc. The separated pure stereoisomeric salts can then be converted by known methods into the corresponding optical isomers of the compounds of formula 16 and the intermediate compounds of formulae 8, 10, 12, 15 or 15. The compounds of formula 1 can be isolated as the free bases, but it is usually more convenient to isolate these compounds as the acid addition salts. These salts are prepared in a conventional manner, for example by treating the free base with a suitable organic or inorganic acid, for example one of the pharmacologically acceptable acids described above. A solution of the base of formula I in a non-reactive solvent such as an alcohol, e.g., methanol or ethanol, or an ether, e.g., diethyl ether, etc., is acidified with a solution of the acid in a similar solvent. The acid solution is added until the salt is completely precipitated. The reaction is carried out at a temperature of 20-50°C, preferably at room temperature. If necessary, the salt can be readily converted to the free base by treatment with a base such as potassium or sodium carbonate or ammonium, potassium or sodium hydroxide. The free base compounds of formula I can be converted to acid addition salts by treatment with a suitable organic or inorganic acid, such as, for example, phosphoric acid, pyruvic acid, hydrochloric acid, sulfuric acid, etc. Typically, the free base is dissolved in a polar organic solvent such as ethanol or methanol and the acid is added to the solution, maintaining the temperature at about 0-100°C. The acid addition salt formed precipitates spontaneously or may be precipitated with a less polar solvent. Acid addition salts of compounds of formula I may be converted to the corresponding free bases by treatment with a suitable base, such as potassium carbonate or sodium hydroxide, usually in the presence of an aqueous solvent at a temperature of about 0-100°C. The free base is isolated by known methods, such as extraction with an organic solvent. Pharmacologically acceptable esters of compounds of formula I and pharmacologically acceptable acid addition salts of these esters are prepared by treating them with an excess of about 1.1 to 2 equivalents of the appropriate acid anhydride or acyl halide in the presence of a catalyst such as pyridine at a temperature of about -10 to +10°C for about 0.5 to 12 hours according to known methods, such as those described in the Examples. Such methods are given in the relevant sections of Morrison and Boyd cited above and in "Reagents for Organic Synthesis", John Wiley and Sonis, Inc., New York, 1967. Suitable esters include acetates, propionates, butyrates, caproates, caprylates, laurates, etc. Pharmacologically acceptable acid addition salts of esters of compounds of formula I are prepared as described in Examples 6, 8 and 9 below. Salts of compounds of formula I can be converted into other salts of compounds of formula I by taking advantage of their various properties, such as solubility and volatility, or by using an appropriately charged ion exchange resin. The transformation is carried out at a temperature from about 0°C to the boiling point of the solvent used in the given process. It has been found that the compounds prepared by the method according to the invention have an effect on calcium entry and β-blockade in animal preparations, using in vitro preparations and animal tissue cultures. Such tests are described, for example, by Kent et al., Federation Proceedings, vol. 40, p. 724 (1981), Killam et al., Federation Proceedings, vol. 42, p. 1244 (1983) and Cotten et al., Journal Pharm. Exp. Therap. vol. 121, pp. 183-190 (1957). It has been found that the compounds of formula I are effective in animal models against cardiovascular diseases, such as arrhythmia, angina and myocardial infarction. These compounds are therefore useful in the treatment of cardiovascular diseases, especially myocardial infarction, angina induced by changes in conditions or exertion, and arrhythmias in mammals, especially in humans. Pharmacological action. 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylamino-carbonylmethyl)-perperazine dihydrochloride was studied for its pharmacological action. 14 The methodology used was given by W. Szekeres, J. Pharm. Exp. Ther, vol. 196, pp. 1-28 (1976), proceeding as described below. Adult dogs of the Bigiel breed weighing 11-16 kg patients were pretreated with 0.2 mg/kg acetylpromazine intramuscularly and anesthetized with 30 mg/kg pentobarbital intravenously. After the injection, oxygen was artificially delivered to the lungs, and the chest was surgically opened through the fifth intercostal space. To obstruct blood flow through the medial ventricular wall, a loose loop was placed on the left anterior descending coronary artery (LAD) using a ligature pulled through the outlet guiding tube. A transient critical narrowing effect of sulcus constriction of the arterial vessel undergoing perfusion below the LAD was induced by periodic (controlled 12-minute time cycles) complete occlusion of the LAD, accelerating the heart rate by 50-70 beats/minute above the resting rate. In each ischemic attack, one minute after the onset of the accelerated heart rate, the LAD was completely occluded with a reversible PETA. The accelerated heart rate and obstruction were maintained for a further 2 minutes. Each ischemic attack resulted in elevated S-T waves on 8 cardiac electrocardiograms. These effects were essentially reversible within 5-10 minutes when spontaneous heartbeat was allowed to return. These S-T wave changes served as an electrophysiological marker during the recovery phase of oxygen-metabolic debt. After the extreme response had been resolved, further cycles of accelerated heartbeat, repeated 4-5 times, were required to bring each heart to a state that allowed for recovery. reproducible, recordable symptoms. The S-T wave elevation induced in this way was always greater than that seen with simple obstruction alone. The study was conducted to determine whether pretreatment with an intravenous cumulative dose of the drug 5 minutes before inducing an accelerated heart rate could prevent S-T wave changes. The results of the study allow us to conclude that the tested compound at an intravenous dose of 5 µg/kg causes a statistically significant reduction in S-T wave height. Other studies have shown that the same compound is characterized by good selectivity in terms of its effect on the myocardium compared to its effect on the vascular muscle, which is a desirable feature of an antianginal drug. 1-[3-(2H-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine and the S-isomer of this compound were administered separately to rats for 7 days at oral doses up to 250 mg/kg/day. No toxic effects were observed for either compound. The active substances, i.e. the compounds of formula I and their salts, can be administered by any route suitable for pharmaceuticals. Suitable methods include oral, parenteral, transdermal, subcutaneous and other systemic methods. Oral administration is preferred. except in cases where the patient cannot take the medication himself. In these cases, parenteral administration may be necessary. Depending on the chosen route of administration, pharmacological agents are formulated as solid, semi-solid or liquid preparations, such as tablets, suppositories, pills, capsules, powders, liquids, suspensions, etc. Preferably, such preparations are unit doses, ensuring the intake of a precisely defined amount of the drug with each administration. Pharmacological agents contain known pharmacological excipients and, as the active substance, a compound of formula 1 or a pharmacologically acceptable salt thereof. They may also contain other drug substances, pharmaceutical agents, carriers, auxiliary substances, etc. The amount of the active substance administered depends, of course, on the patient being treated, his weight, The effective dose, however, is 0.1-10 mg/kg/day, preferably 0.5-5 mg/kg/day. For an average patient weighing 70 kg, the daily dose is 7-700 mg, preferably 35-350 mg. Since all the effects of the compounds of formula IN (anti-infarction effect, inhibition of angina caused by changes in conditions or exertion, and antiarrhythmic effect) result from a similar mechanism (blocking calcium entry), the doses and routes of administration are within the same general and preferred ranges for all these applications. For the production of solid preparations, known non-toxic solid carriers can be used, e.g., also pharmaceutically pure substances such as mannitol, lactose, starch, magnesium stearate, o-sulfobenzoic acid imide sodium salt, talc, cellulose, glucose, sucrose, magnesium carbonate, etc. The active ingredient can be formulated as suppositories using, for example, polyalkylene glycols such as propylene glycol as carriers. Liquid pharmaceutical preparations can be prepared by dissolving, dispersing, etc. the active ingredient and optionally auxiliary substances in a vehicle such as water, saline, aqueous dextrose, glycerin, ethanol, etc., to form a solution or suspension. If desired, the pharmaceutical preparation can also contain minor amounts of non-toxic auxiliary agents such as wetting agents, emulsifiers, buffers, etc. Examples of such agents are sodium acetate, sorbitan monolaurate, sodium triethanolamine acetate, oleate. Triethanolamine, etc. Methods for preparing such preparations and their forms are known to those skilled in the art or can be found, for example, in Remington's "Pharmaceutical Sciences", Mack Publishing Company, Easton, Pennsylvania, 15th ed., 1975. In each case, the preparation to be administered containing the active ingredient, i.e., the compound of formula I, contains it in an amount effective to alleviate the symptoms occurring in the patient to be treated. For oral administration, pharmacologically acceptable non-toxic compositions containing pharmaceutically pure excipients such as, for example, mannitol, lactose, starch, magnesium stearate, sodium o-sulphobenzoic acid imide, talc, cellulose, glucose, sucrose, magnesium carbonate, etc. These agents are prepared in the form of solutions, suspensions, tablets, pills, capsules, powders, slow-release preparations of the active substance, etc. Such preparations may contain 10-95 µg/t, preferably 1-70 µg/t of the active substance. In the case of parenteral administration, the drug is injected subcutaneously, intramuscularly, or intravenously. Injectables are prepared in the form of known preparations, such as liquid solutions or suspensions, solid preparations for preparing solutions or suspensions in liquid immediately before injection, or emulsions. Suitable excipients are, for example, water, saline, dextrose, glycerin, ethanol, etc. In addition, if necessary, the pharmacological agents may contain small amounts of non-toxic auxiliaries such as wetting agents, emulsifiers, buffers, etc. Examples of such agents are sodium acetate, sorbitan monolaurate, triethanolamine laurate, etc. A recently introduced method of parenteral administration consists in implanting a system for slow or sustained release of the active substance, ensuring the achievement of a constant dose level, as described, for example, in U.S. Patent No. 3,710,795. The invention is illustrated by the following examples, in which the abbreviation "mp" denotes melting point, wherein Examples I-III relate to the preparation of starting materials and Examples IX-X relate to the preparation of products. Example I. (a) To a solution of 76 g of 2-methoxy- phenol in about 60 ml of water and 200 ml of dioxane containing 29 g of sodium hydroxide is slowly added 80 g of epichlorohydrin (large excess). The solution is stirred at reflux for 3 hours. The mixture is diluted with ether, washed with two 50 g portions of water and dried over anhydrous magnesium sulfate. Evaporation of the anhydrous extract and distillation of the residue gives 1-(2-methoxyphenoxy)-2,3-epoxypropane. Cb) Proceed as in (a) above, but using a stoichiometric equivalent amount of 2-methylphenol, 3-methylphenol, 4-methylphenol, 4-n-butylphenol^ 2Hmethoxyphenol, 4-methoxyphenol, 2-isopropoxyphenol, 2sn-butoxyphenol, 2-chlorophenol, 4-cWo-phenol. 4-Bromophenol, 2,4-Dimethylphenol, 2,4-Dichlorophenol, 4-Methyl-5-chlorophenol, 3,4,5-Trichlorophenol, 3,4,5-Trimethoxyphenol, 3-Methyl-4-chloro-5-methoxyphenol, 3,4,5-Tetrabromophenol, 3,6-Dimethyl-4,5-dichlorophenol, 4-Trifluoromethylphenol, 142 760 1T 18 20 25 30 4-Methylthiophenol, 4-n-Butylthiophenol, 4-n-Methylstilfinylphenol, 4-n-Butylsulfinylphenol, 4-methylsulfonylphenol, 4-butylsulfonylphenol, 2-cyanophenol, 2-acetylenol, 4-n-butyrylenol, 4-(N-N-dimethylamino)phenol, 4-(N-N-di-n-butyflamino)phenol, 1-naphthol, thiophenol or 4-methylphenylthiol the following epoxy compounds of formula 10 are obtained: 1-(2-methylphenoxy)-2,3-epoxypropane, 1-{3-methylphenoxy)-2,3-epoxypropane, 1-(4-methylphenoxy)-2,3-epoxypropane, 1-(4-n-butylphenoxy)-2,3-epoxypropane, 1-(2-methoxyphenoxy)-2,3-epoxypropane, 1-(4-methoxyphenoxy)-2,3-epoxypropane, 1-(2-isopropoxiphenoxy)-2,3-epoxypropane, 1-(4-chlorophenoxy)-2,3-epoxypropane, 1-(2-chlorophenoxy)-2,3-epoxypropane, 1-(4-chlorophenoxy)-2,3-epoxypropane, 1-(4-chlorophenoxy)-2,3-epoxypropane, 1-(4-bromophenoxy)-2,3-epoxypropane, 1-(2,4-dimethylphenoxy)-2,3-epoxypropane, 1-(2,4-dichlorophenoxy)-2,3-epoxypropane, 1-(4-methyl-5-chlorophenoxy)-2,3-epoxypropane, 1-(3,4,5-trichlorophenoxy)-2,3-epoxypropane, 1-(3,4,5-trimethoxyphenoxy)-2,3-epoxypropane, 1-(3-methyl-4,5-dichlorophenoxy)-2-epoxypropane, 1-(3-methyl-4-chloro-5-methoxyphenoxy)-2,3-epoxypropane, 1-(2,3,4,5-tetrabromophenoxy)-2,3-epoxypropane, 1-(3,6-dimethyl-4,5-dichlorophenoxy)-2,3-epoxypropane, 1-(4-trifluoromethylphenoxy)-2,3-epoxypropane, 1-(4-methylthiophenoxy)-2,3-epoxypropane, 1-(4-n-butylphenoxy)-2,3-epoxypropane, 2-(4-n-methylsulfinylphenoxy)-2,3-epoxypropane, 1-(4-n-butylsulphinylphenoxy)-2,3-epoxypropane, 1-(2-cyanophenoxy)-2,3-epoxypropane, 1-(2-acetylphenoxy)-2,3-epoxypropane, 1-(4-n-butyrylphenoxy)-2,3-epoxypropane, 1-[4-(N,N-dimethylamino)enoxy]-2,3-epoxypropane, 1-[4-N,N-dimethylamino)phenoxy]-2,3-epoxypropane, 1-(1-naphthoxy)-2,3-epoxypropane, 1-phenylthio-2,3-epoxypropane or 1-(4-methylphenylthio)-2,3-epoxypropane. The compounds obtained are sufficiently pure to be used in further reactions. (c) By proceeding in a similar manner to (a) of this example, but using a stoichiometrically equivalent amount of S-epichlorohydrin instead of epichlorohydrin, R-1-(2-methoxyphenoxy)-2,3-epoxypropane is obtained in good yield. (e) By proceeding in a similar manner to (a) of this example, but using a stoichiometrically equivalent amount of the above-mentioned substituted phenol instead of 2H-methoxyphenol, the corresponding (R)-substituted-phenoxy) epoxide compounds of formula 10 are obtained. (e) By proceeding in a similar manner to (a) of this example, but using a stoichiometrically equivalent amount of R-epichlorohydrin instead of epichlorohydrin, the corresponding (S)-1-(2-methoxyphenoxy)-2,3-epoxypropane is obtained in good yield. (f) By proceeding similarly to (e) of this Example, but using a stoichiometrically equivalent amount of R-epichlorohydrin instead of epichlorohydrin and a substituted phenol instead of 2nmethoxyphenol, the corresponding (S)-1-substituted-phenoxy-2,3-epoxypropane is obtained in good yield. (g) By proceeding similarly to (a), (b), (c), (d), (e) or (i) above, but using a stoichiometrically equivalent amount of an optionally substituted phenylthiol derivative in place of 2-methoxyphenol, the corresponding R-,S- or R,S- 1-(optionally substituted -phenylthio)-2,3-epoxypropane is obtained. Example 2. Preparation of (2,6-dimethylphenyl)aminocarbonylmethyl chloride. (a) 96 g (793 mmol) of 2,6-dimethylaniline and 96 g (130 ml) of triethylamine are dissolved in 1 liter of methylene chloride. The mixture was cooled in ice and 89.6 g (800 mmol) of chloroacetyl chloride was slowly added. The mixture was stirred for 4 hours until the reaction mixture became very dark. The mixture was washed with dilute hydrochloric acid and concentrated in vacuo. Hexane was then added, precipitating the product, (2,6-dimethylphenyl)aminocarbonylmethyl chloride. The crude product was filtered, washed, and dried, yielding 130 g of material of sufficient purity for use in subsequent reactions. (b) Proceeding in a similar manner to the above, but using in place of 2,6-dimethylaniline a stoichiometrically equivalent amount of aniline, 2-chloroaniline, 3-chloroaniline, 4-chloroaniline, 2-bromoaniline, 4-chromoaniline, 2-fluoroaniline, 3-fluoroaniline, 4-fluoroaniline, 2-methylaniline, 3-methylaniline, 4-methylaniline, 4-n-methylaniline, 2-methoxyaniline, 3-methoxyaniline, 4-methoxyaniline, 4-n-butoxyaniline, 2-trifluoromethylaniline, 3-trifluoromethylaniline, 4-trifluoromethylaniline, 2,6-dichloroaniline, 3,5-dimethoxyanilines, 3,4-methylenedioxyanilines, 2-chloro-5-methylanilines, 4-methylthioanilines, 4-methylsulfinylanilines, 4-methylsulfonylanilines, 4-n-butylthioanilines, 4-n-butylsulfinylanilines, 4-n-butylsulfonylanilines, 3,4-difluoroanilines, 4-chloro-3-trifluoromethylanilines, 4-n-fluoro-3-trifluoromethylanilines, 2,5-diethoxyanilines, 2,4-trichloroanilines, 3,4,5-trimethoxyanilines, 2,4,5,6-tetrachloroanilines, 2,3,4,6-tetramethylanilines, 2,3,4,5,6^ five chloroanilines, 3-chloro-2,4^-trimethylaniline, 2-cyanoaniline, 4-(acetamido)-anilkyl, 4^(N-methicacetamido)aniline, 4-(N-n-butylacetaniido)amline, N-methylaniline, N^n^butylaniline, NHmethyl-2,6-dimethylaniline or N-n-butyl-2,6-dimethylaniline, the following substituted chlorides of formula 15 are obtained: phenylaminocarbonylmethyl chloride, 2-chlorophenylaminocarbonylmethyl chloride, 3-chlorophenylaminocarbonylmethyl chloride, chloride 4-chlorophenylaminccarphoonylmethyl chloride 2-Bromophenylaminocarbonylmethylmethyl chloride, 3-Bromophenylaminocarbonylmethyl chloride, 4-Bromophenylaminocarbonylmethyl chloride, 2-Fluorophenylaminocarbonylmethyl chloride, 3-Fluorophenylaminocarbonylmethyl chloride, 4-Fluorophenylaminocarbonylmethyl chloride, t-Methylphenylaminocarbonylmethyl chloride, 3-Methylphenylaminocarboxylic acid chloride, 4 ... 2H^cioic«yf»ykamiiK))tarlonylmethylm©iyKi, 3-phenethoxyphenylaminocarbonylmethyl chloride, 4-(4-methylphenylaminocarbonylmethyl chloride), 4-(4-methylphenylaminocarbonylmethyl chloride), 3-(4-methylphenylaminocarbonylmethyl chloride), 4 ... 3,4-Ethyldimethylaminocarboxymethyl chloride, 2-Hydroxy-4H-methylphenylcarboxymethyl chloride, 4-Tricthiophenylaminocarboxymethyl chloride, 4-Methylsulfinylphenylaminocarbonylmethyl chloride, 4-Methylsulfinylphenylaminocarbonylmethyl chloride, 4-Methylsulfonylphenylaminocarbonylmethyl chloride, 4-N-Triethylthiophenylaminocarbonylmethyl chloride, 4-N-Butylmethylphenylaminocarbonylmethyl chloride, 4-N-Trifluorophenylaminocarbonylmethyl chloride, 3-N-Trifluorophenylaminocarbonylmethyl chloride 4-chlorotrifluoromethylphenylaminocarbonylmethyl chloride, 4-fluorotrifluoromethylphenylaminocarbonylmethyl chloride, 2,5-diethoxyphenylaminocarbonylmethyl chloride, 3,4,5-trimethoxyphenylaminocarbonylmethyl chloride, 2,4,5,6-tetrachlorophenylaminocarbonylmethyl chloride, 4-fluoromethylphenylaminocarbonylmethyl chloride, 2,5-trichlorophenylaminocarbonylmethyl chloride, 3^chloro^47«-trimethylenemyenecarbonylmethyl chloride, ^yJM^ienylBminocarbonylmethyl chloride, 4^cetemlda*anykamiilacarboaylmethylmctylur cfckrek 4^HnetyioeceiienLdoienyllamkiocarboay- kraetite chloride 4-N-n-b'tylOflK'tamidofeiiylmethylk)carbonylmethyl chloride, N-methyl-N-teiyk'iniiM)kATbonylmethyl-tyiu chloride, M-'-l)utyl-N-teiyk)eneMnocaxbonylmethyl chloride, K-1)9elyl*N-2^dimethylphenylamiiocarbonylmethyl or chloride N-4-ethyl-N-dimethylaminocarboxymethylmethyl chloride of sufficient purity for use in subsequent reactions, (c) By proceeding in a similar manner to that in (but using stoichiometrically equivalent amounts of 2-chloropropionyl chloride, 2-chloro-n-butyryl chloride, or 2-chlorocaprol chloride in place of 2-chloroacetyl chloride, the following substituted chlorides of formula 15 are obtained: 1,6-Kivumethyphenylacetatecarbonyl-1-ethyl chloride, 2,6-Dimethylphenylaminocarbonyl-1-n-propyl chloride, or 2,6-Dimethylphenylaminocaprotyl-1-n-ethyl chloride. -pentyl. (d) By proceeding in a similar manner to that of (a), but using a stoichiometrically equivalent amount of aniline, N-methyl-2,6-dimethylaniline, or N-methyl-2,6-dimethylaniline instead of 2,6-dimethylaniline, and 2-chloropropionyl chloride instead of chloroacetyl chloride, there are obtained, respectively, phenylaminocarbonyl-1-ethyl chloride, N-methyl-N-2,6-dimethylphenylaminocarbonyl-1-ethyl chloride, or N-butyl-N-2,6-dimethylphenylaminocarbonyl-1-ethyl chloride. (e) By proceeding in a similar manner to that of (a), but using a stoichiometrically equivalent amount of aniline, N-2,6-dimethylaniline or N-n-butyl-2,6-dimethylaniline instead of 2,6-dimethylanthline and 2-chloro-n-caproyl chloride instead of chloroacetyl chloride, respectively: phenylaminocarbonyl-1-n-pentyl chloride, N-methyl-N-2,6- carbonyl-1-n-pentyl or N-n-butyl-N-2,6-methylphenylamino-1-n-pentyl chloride. Example III. Preparation of 1-[3-<2-methoxy-phenoxy)-2-hydroxypropyl]piperazine. (a) In 500 ml of ethanol were dissolved 45 g (0.25 mole) of crude (2-methoxyphenoxy)-2,3-epoxypropane, prepared in Example 1, and 86 g (1 mole) of piperazine. The mixture was kept at room temperature for 2 days, then evaporated, and the product was isolated by adding ammonia to the residue and extracting with methyl chloride. After adding ether, the product crystallized and filtered. The resulting crude mixture was boiled with ether and then evaporated. The residue was triturated with hexane to give pure 1-[3-(2-methoxyphenoxy-2-hydroxypropyl]piperazine. Proceeding in a similar manner to (a) above, but using in place of 2,6-[(2-methylphenylaminocarbonylmethyl chloride] a stoichiometrically equivalent amount of: 1-(2-methylphenoxy)-2,[3-epoxypropene], 1-[(4-methylphenoxy)-2,[3-epoxypropane], 1-[(4-methoxyphenoxy)-2,[3-epoxypropane], 1-[(4-methoxyphenoxy)-2,[3-epoxypropane], 1-[(2-isopropoxylenoxy)-2,[3-epoxypropane], 1-(2-butoxylenoxy)-2,3-epoxypropane, 1-(4-chloroethioxy)-2,3-epoxypropane, 2,4-methylphenoxy)-2,3-epoxypropane, 2,4-dichlorophenoxy)-2,3-epoxypropane, 1-(3,4-trimethylphenoxy)-2,3-epoxypropane, 1-(3-methyl-4-chloro-5-methoxyphenoxy)-2,3-epoxypropane, 2,3,4,5-tetrabromophenoxy)-2,3-epoxypropane, 1-(2,6-dimethyl-3,4-dichlorophenoxy)-2,3-epoxypropane, 1-(4-trifluoromethylphenoxy)-2,3-epoxypropane, 1-(4-methylthiophenoxy)-2,3-epoxypropane, 1-(4-methylsulfinylphenoxy)-2,3-epoxypropane, 1-(4-methylsulfinylphenoxy)-2,3-epoxypropane, 1-(4-methylthiophenoxy)-2,3-epoxypropane, 1-(4-methylthiophenoxy)-2,3-epoxypropane, 1-(4-methylthiophenoxy)-2,3-epoxypropane, 1-(2-acetylphenoxy)-2,3-epoxypropane, 1-(4-n-butyrylphenoxy)-2,3-epoxy, 1-(4-aminocarbonylmethylphenoxy)-2,3-epoxypropane, 4-N,N-dimethylaminophenoxy)-2,3-epoxypropane, 1-(4-N,N-di-n-butylammophenoxy)-2,3-epoxypropane, 1-(1-naphthoxy)-2,3-epoxypropane, 1-(phenylthio)-2,3-epoxypropane or 1-(4-methylphenylthio)-2,3-epoxypropane the following piperazines are obtained: 1-[3-(2-methylphenoxy)-2-hydroxypyrropyl]piperazine, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]piperazine, 1-[3-(2-chlorophenoxy)-2-hydroxypropyl]piperazine, 1-[3H(2-bromophenoxy)-2-hydroxypropyl]piperazine, 1-[3-(4-methylphenoxy)-2-hydroxypropyl]piperazine, 1-[3-(4-methoxyphenoxy)-2-hydroxypropyl]piperazine, 1-[3-(2-isopropoxyphenoxy)-2-hydroxypropyl]piperazine, 1-[3-(2-n-butoxyphenoxy)-2-hydroxypropyl]piperazine, 1-[3-(4-chlorophenoxy)-2-hydroxypropyl]piperazine, 1-[3-(2,4-dimethylphenoxy)-2-hydroxypropyl]piperazine, 1-[3-(2,4-dichlorophenothyl)-2-hydroxypropyl]piperazine, 1-[3-(3,4,5-trichlorophenoxy)-2-hydroxypropyl]piperazine, 1-[3-(3-methylchlorophenoxy)-2-hydroxypropyl]piperazine, 1-[3-(3-methylchlorophenoxy)-5-trimethylphenothyl]piperazine, 1-[3-(2,3,4,5-tetrabromophenoxy)-2-hydroxypropyl]piperazine, 1-[3-(2,6-dimethyl-3,4-dichlorophenoxy)-2-hydroxypropyl]piperazine, 1-[3-(4-trifluoromethyl)-2-hydroxypropyl]piperazine, 1-[3-(4-methylthiophenoxy)-2-hydroxypropyl]piperazine, 1-[3-(4-n-butylsulfonylphenoxy)-2-hydroxypropyl]piperazine, 1-[3-(4-n-butylthiophenoxy)-2-hydroxypropyl]piperazine, 1-[3-(4-n-butylthiophenoxy)-2-hydroxypropyl]piperazine, 1-[3-(4-n-butylsulfonylphenoxy)-2-hydroxypropyl]piperazine, 1-[3-(2-acetylphenoxy)-2-hydroxypropyl]piperazine, 1-[4-(4-n-butyrylphenoxy)-2-hydroxypropyl]piperazine, 1-[3-(4-aminocarbonylmethyl(phenoxy)-2-hydroxypropyl]piperazine, 1-[3-(4-N,N-dimethylaminophenoxy)-2-hydroxypropyl]piperazine, 1-[3-(4-N,N-di-n-butylaminophenoxy)-2-hydroxypropyl]piperazine, 1-[3-(1-naphthoxy)-2-hydroxypropyl]piperazine, 1-[3-{phenylthio)-2-hydroxypropyl]piperazine or 1-[3-(4-methylphenylthio)-2-hydroxypropyl]piperazine. (c) Proceeding in a similar manner to (a) above, but using a stoichiometrically equivalent amount of R-3-(2-methoxyphenoxy)-2,3-epoxypropane in place of 3-(2-methoxyphenoxy)-2,3-epoxypropane, gives R-1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]piperazine. (d) By proceeding in a similar manner to (a), but using a stoichiometrically equivalent amount of one of the R-substituted phenoxy-2,3-epoxypropanes mentioned in (b) of Example 1 in place of 1-(2-methoxyphenoxy)-2,3-epoxypropane, the corresponding R-[3-(substituted-phenoxy)-2-hydroxypropyl]di)azine is obtained. (e) By proceeding in a similar manner to (a), but using a stoichiometrically equivalent amount of S-1-(2-methoxyphenoxy)-2,3-epoxypropane instead of M-(2-methoxyphenoxy)-2,3-epoxypropane, the corresponding S-1-(3-(2-methoxyphenoxy)-2-hydroxypropyl)piperazine is obtained. (f) By proceeding in a similar manner to (a), but using a stoichiometrically equivalent amount of any 3-(3-(substituted-phenoxy)-2,3-epoxypropane) from the compounds listed in (a) or (f) of Example 1 in place of 1-(2-methyl-phenoxy)-2,3-epoxypropane, the corresponding S-1-(substituted-phenoxy)-2-hydroxypropyl]papierazine is obtained. (g) By proceeding in a similar manner to (a), but using a stoichiometrically equivalent amount of a mixture of any R- and S-unsubstituted or aryl-substituted-1-enoxy-2,3-epoxypropane from the compounds listed in (a) or (f) of Example 1 in place of 1-(2-methyl-phenoxy)-2,3-epoxypropane, the corresponding S-1-(substituted-phenoxy)-2-hydroxypropyl]papierazine is obtained. 1-(unsubstituted or aryl-substituted-phenoxy-hydroxypropyl)-piperazine is obtained. Example IV, Preparation of 1-[3-(2-methoxy-phenoxy)-2-hydroxypropyl]-4H-(2,6-dimethylphenylaminocarbonylmethyl)piperazine. (a) 12 g (35 mmol) of 2,6-dimethylenylaminocarbonylmethyl chloride from point (a) and 15 g (65 mmol) of 1-(3-(2-methoxyphenoxy)-2-hydroxypropyl)piperazine from point (a) of Example 3P are mixed with 100 ml of dimethylformamide. The mixture is stirred at 65°C until the components are dissolved, and then at 90°C overnight. The entire mixture is added to water and acidified with hydrochloric acid. The resulting homogeneous mixture is washed with ether, basified with ammonia, and extracted with three portions of methylene chloride. The organic extracts containing the product are The oil was washed twice with water and evaporated to give 28 g of oil. The oil was purified by chromatography on 500 g of silica gel using a 5% solution of methanol in methylene chloride. 20 g of the yellow oil obtained was dissolved in methanol and hydrochloric acid was added, which led to crystallization. After complete precipitation by adding ether, 16 g of the product were obtained, i.e., 1-[3-(2-methoxypropoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine, as an oil. Due to the undefined stereoisomerism of the carbon atom in position 2 of the 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]piperazine chain of Example 3, this compound The substituted compounds listed in (o), (c) and (d) below are obtained as mixtures of the R and S isomers. (b) By proceeding similarly to (a) above, but using a sclechiometrically equivalent amount of the appropriate substituted chloride instead of 2,6-dimethylphenylaminocarboxymethyl chloride, the corresponding 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-2-(substituted-phenylacemocarbonylmethyl)piperazine is obtained. Examples of these compounds are: 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(phenylaminocarbonylmethyl)piperazine, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(phenylaminocarbonylmethyl)piperazine, (4-chlorophenylaminocarbonylmethylpiperazine, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(4-methylphenylaminocarbonylmethyl)piperazine, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(4-methoxyphenylaminocarbonylmethyl)piperazine, 1-[2-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(4-methoxyphenylaminocarbonylmethyl)piperazine, 1-[3-(2-methoxylenoxy)-2-hydroxypropyl]-4-(3-chlorophenylaminocarbonylmethyl)piperazine, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4- (2,6-Dichlorophenylthiocarbcylmethyl)piperazine, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,4,6-trimethylphenylaminocarbonylmethyl)piperazine, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(3,4,5-dimethoxyphenylaminocarbonylmethyl)piperazine, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(4-methylthiophenylaminocarbonylmethyl)piperazine, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(4-ethylthiophenylaminocarbonylmethyl)piperazine, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(4-methylsuvinylphenylaminocarbonylmethyl)piperazine, 1-[3-(2-methoxyphenyl)-2-hydroxypropyl]-4-(4-n-propylsulfinylphenylaminocarbonylmethyl)piperazine, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(4-trifluoromethylphenylaminocarbonylmethyl)piperazine, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2-chloro-5-methylphenylaminocarbonylmethyl)piperazine, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2-chloro-5-methylphenylaminocarbonylmethyl)piperazine, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(4-n-propylsulfinylphenylaminocarbonylmethyl)piperazine (3,5-dichlorophenylaminocarbonylmethyl)piperazine, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-diethoxyphenyl)aminocarbonylmethyl)piperazine, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(3-bromo-4-methylphenylaminocarbonylmethyl)piperazine, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(4-n-butylphenylaminocarbonylmethyl)piperazine and 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-(4-isobutylphenylaminocarbonylmethyl)piperazine. (c) Proceeding in a similar manner to (a) above, but using a stoichiometrically equivalent amount of any substituted piperazine from the compounds listed in (b) of Example 3 in place of 1-[3-(substituted-(phenoxy)-1-(2-hydroxypropyl)-4-(2-dimethylphenylaminocarbonylmethyl)piperazine, the corresponding 1-[3-(substituted-(phenoxy)-1-(2-hydroxypropyl)-4-(2-dimethylphenylaminocarbonylmethyl)piperazine is obtained. Examples of these compounds are: 1-[3-(4-methylphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine, 1-[3-(4-methoxyphenoxy)-2-hydroxypropyl]-4-(2-hydroxypropyl)-4-(2 ... -(2,6-dimethylphenylaminocarbonylmethyl)piperazine, 1-[3-(4-chlorophenoxy)-2-hydroxypropyl]-4- -(2,6-dimethylphenylaminocarbonylmethyl)piperazine, 1-[3-(3-methylphenoxy)-2-hydroxypropyl]-4- -(2,6-dimethylphenylaminocarbonylmethyl)piperazine, 1-[3-(3-methoxyphenoxy)-2-hydroxypropyl]-4- -(2,6-dimethylphenylaminocarbonylmethyl)piperazine, 1-[3-(4-methoxyphenoxy)-2-hydroxypropyl]-4- -(2,6-dimethylphenylaminocarbonylmethyl)piperazine, 1-[3-(2,4-dimethylphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine, 1-[3-(2-acetylphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine, 1-[3-(4-aminocarbonylmethylphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine or 1-[3-(1-naphthoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine. (d) Proceeding as in (a) above, but using a stoichiometrically equivalent amount of any chloride from the compounds described in Example 2 instead of 2,6-dichloride? methylphenylaminocarbonylmethyl)piperazine and using a stoichiometrically equivalent amount of any substituted piperazine from the compounds described in (b) of Example 3 in place of 1-[3-(2-methyl-phenoxy)-2-hydroxypropyl]-piperazine gives the corresponding 1-[3-(substituted-phenoxy)-2-hydroxypropyl]-substituted-phenylaminocarbonylalkyl]-piperazine. Examples of these compounds are: 1-[3-(4-methylphenoxy)-2-hydroxypropyl]-4-(phenylaminocarbonylmethyl)piperazine, 1-(chlorophenoxy)-2-hydroxypropyl]-4-(4-chloro- 1-[3-(3-methylphenoxy)-2-hydroxypropyl]-4-(4-methylphenylaminocarbonylmethylpiperazine, 1-[3-(4-methoxyphenoxy)-2-hydroxypropyl]-4-(4-methamethoxyphenylaminocarbonylmethyl]-1-[3-(2,4-dimethylphenoxy)-2-hydroxypropyl]-4-(4-chlorophenylaminocarbonylmethyl)piperazine, 1-[3-(3-methoxyphenoxy)-2-hydroxypropyl]-4-(3-chlorophenylaminocarbonylmethyl)piperazine, 1-[3-(4-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-methylphenylaminocarbonylmethyl)piperazine, 1-[3-(4-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-methylphenylaminocarbonylmethyl)piperazine, 1-[3-(3-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-methylphenylaminocarbonylmethyl)piperazine, 1-[3-(4 ... -dichlorophenylaminocarbonylmethylpiperazine, 1-[3-(4-methoxyphenoxy)-2-hydroxypropyl]-4-(2,4,6-trimethylphenylaminocarbonylmethylpiperazine, 1-[3-(4-methylthiophenoxy)-2-hydroxypropyl]-4-(3,5-dimethoxyphenylaminocarbonylmethyl)piperazine, 1-[3-(2-chlorophenoxy)-2-hydroxypropyl]-4-(4-methylthiophenylaminocarbonylmethyl)piperazine, 1-[3-(2-methylphenoxy)-2-hydroxypropyl]-4-(4-ethylthiophenylaminocarbonylmethyl)piperazine, -1[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(4-methyl5ulfinylphenylaminocarbonylmethyl)piperazine, 1-[3-(4-trifluoromethylphenoxy)-2-hydroxypropyl]-4-(4-n-butylsulfinylphenylaminocaribonylmethyl)-piperazine, 1-[3-(2-methylphenoxy)-2-hydroxypropyl]-4-<4-trifluoromethylphenylaminocarbonylmethyl)-piperazine, 1-[3-(2-methylsulfkylphenoxy)-2-hydroxypropyl]-4-(2-chloro-5-methylphenylmethyl)-piperazine, l-[3-(4-methylsulfonylaphenoxy)-2-hydroxypropyl- lo]-4^(3,5-difluorophenylaminocarbonylmethyl)-piperazine, " 1-[3-(4-n-butylsulfiniophenoxy)-2-hydroxypropyl]-4-(2,6-diethoxyphenylaminocarbonylmethyl)piperazine, 1-[3-(4-methoxyphenoxy)-2-hydroxypropyl]-4-(3-bromo-4-ethylphenylaminocarbonylmethylpaperazyoa, - 1-P^4nmethylthioiphenoxy)-2-hydroxypropylI-4-(4--n-butylphenylaminocarbonylmethyiIo)piperazine, l-^-^HmethoxyphenoxyJ-a-hydro^ (4-isobutylphenylaminocar^^^ na, 1-[3-(4-n-butylthiophenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaphninecarbonylmethyl)piperazine, 1-[3^2-inetyl-3l4*dfwuehIorota*)te propyl]-4-<2,6-dimethylphenylanT«iocarbonyl« methyl)-piperazine, 1-[3-(2,3,4^-c2terochk)rophenoxy)-2-hyite«kflyp!ropyl]^^2,6-dimethylphenykaf]fiijw)carbonyk)methyl)-5 piperazine, 1-[3-(2-methyl-5^hkxrofet*oxy)-2~h^ 1-[3-(4-n-butylsulfinylphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine, 1-[3-(4-n-butylsulfonylphenoxy)-2-hydroxypropyl]-(2,6-dimethylphenylaminocarbonylmethyl)piperazine, 1-[3-(4-n-butylsulfonylphenoxy)-2-hydroxypropyl]-(2,6-dimethylphenylaminocarbonylmethyl)piperazine, 1-[3-(2,4-dimethylphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine, 1-[3-(1-naphthoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine, 1-[3-(2H-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonyl-1-ethyl)piperazine, 1-[3-(2H-methoxyphenoxy)-2-hydroxypropyl]-4-(N-methyl-N-2-dimethylphenylaminocarbonyl-1-ethyl)piperazine, 1-[3-(2H-methylphenoxy)-2-hydroxypropyl]-4-(N-methyl-N-2-dimethylphenylaminocarbonyl-1-ethyl)piperazine, 30 1-(3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonyl-1-n-pentyl)piperazine, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(N-methyl-N-2,6-dimethylphenylaminocarbonyl-1-n-pentyl)piperazine, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(N-n-methyl-N-2,6-dimethylphenylaminocarbonyl-1-n-pentyl)piperazine, 1-[3-(1-phenylthio)-2-hydroxypropyl]-4-(1-phenylaminocarbonylmethyl)piperazine or 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(phenylaminocarbonylmethyl)piperazine. (e) Proceeding similarly to (a) above, but using a stoichiometrically equivalent amount of any substituted R-1-(phenoxy-2-hydroxypropyl)piperazine from the compounds described in Example 3 in place of 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]piperazine and using a stoichiometrically equivalent amount of any substituted phenylaminocarbonylmethyl chloride from the compounds described in Example 2 in place of 2,6-dimethylphenylaminocarbonylmethyl chloride, the corresponding R-1-[3-substituted-phenoxy)-2-hydroxypropyl]-4-substituted-phenylaminocarbonylmethyl]piperazine. (£) By proceeding similarly to (a) above, but using the appropriately substituted R-isomer of piperazine instead of 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]piperazine, the following compounds of R configuration are obtained: 1-[3-(2-methylphenoxy)-2-hydroxypropyl]-4-(2-dimethylphenylaminocarbonylmethyl]piperazine, 1-[3-(2-methoxyphenoxy)-2-dimethylphenylaminocarbonylzine, 1-[3-(2-chlorophenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine, 1-[3-(3-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine, 1-[3-(3-chlorophenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine, 1-[3-(3-chlorophenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine and 1-[3-(2,4-dimethylphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine (2,6-dimethylphenylaminocarbonylmethyl)piperazine. Additional examples of compounds which can exist in the R-isomer form are listed in (g). Proceeding similarly to (a) above, but using a stoichiometrically equivalent amount of 1-[3-(substituted-phenoxy)-2-hydroxypropyl]piperazine in the S-isomer form or any substituted piperazine in the S-isomer form from the compounds listed in (f) of Example 3 in place of 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]piperazine, and using a stoichiometrically equivalent amount of any substituted phenylaminocarbonyl chloride from the compounds listed in (b) of Example 3. II instead of 2,6-dimethylphenylaminocarbonylmethyl chloride, the corresponding S-1-[3-substituted-phenoxy)-2-hydroxypropyl]-4-(substituted-phenylaminocarbonyl)piperazine is obtained. Additional examples of compounds which may be a mixture of the R and S forms are listed in parts (b), (c), (d), (e) and (f) of this Example. (h) Proceeding similarly to part (a) above, but using a stoichiometrically equivalent amount of a mixture of the R and S isomers or any R- and S-substituted-1-[3-(substituted-phenoxy)-2-hydroxypropyl]-piperazine from the compounds listed in part (g) of Example III instead of 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]- piperazine and using a stoichiometrically equivalent amount of any substituted phenylaminocarbonylmethyl chloride from the compounds listed in (b) of Example II in place of 2,6-dimethylphenylaminocarbonylmethyl chloride, the corresponding mixture of R- and S-forms of 1-[3-substituted-phenoxy]-2-hydroxypropyl]-4-substituted-phenylaminocarbonylmethylpipetazine is obtained. Additional examples of compounds which may be a mixture of the R- and S-forms are listed in (f), (c), (d), (e) and (f) of this Example. Example V. Compounds of formula I are prepared according to the procedure of Example IV, and the hydrochlorides or dihydrochlorides of the compounds listed below can be prepared according to the procedure of example VI. If necessary, these exemplary compounds and salts can be converted to the free bases by reacting with X or another salt as described in Example 8. The following compounds are obtained: 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(phenylaminocarbonylmethyl)piperazine and its dihydrochloride, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(4-chlorophenylaminocarbonylmethyl)piperazine and its dihydrochloride, 1-[3-(2-cyanophenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine and its dihydrochloride. dihydrochloride, m.p. 213-215°C, 1-[3-(2H-methoxyphenoxy)-2-hydroxypropyl]-4-(2-methoxyphenylaminocarbonylmethyl)piperazine and its dihydrochloride, 1-[3-(2H-methoxyphenoxy)-2-hydroxypropyl]-4-(3,4-dichlorophenylaminocarbonylmethyl)piperazine and its dihydrochloride, R-1-[3-(2H-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine and its dihydrochloride, m.p. 220-222°C, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4- (3,5-dimethoxyphenylaminocarbonylmethyl)piperazine and its dihydrochloride, R,S-1-[3-(4-chlorophenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine and its dihydrochloride, m.p. 205°C, R,S-1-(3-phenoxy-2-hydroxypropyl)-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine and its dihydrochloride, m.p. 195°C, R,S-1-(3-phenoxy-2-hydroxypropyl)-4-(2,5-dimethylphenylaminocarbonylmethyl)piperazine and its dihydrochloride, m.p. 167°C, R^-1-[3n(3,4,5-trimethoxyphenoxy)-2-hydroxypropyl)-4-(2,6-dimethylphenylaminocarbonylmethyl]^piperazine and its dihydrochloride, mp 210°C, R,S-1-[3-(2-methoxyphenolsy)-2^hydroxypropyl]- 4-(3,4-dichlorophenylaminocarbonylmethyl)piperazine and its dihydrochloride, mp 192°C, R,S-1-[3-(2-acetylphenoxy)-2-hydroxypropyl]- 40 4-(2,6-dimethylphenylaminocarbonylmethyldpiperazine and its dihydrochloride, mp 195°C, R,S-1[3-(4-aminocarfoonylmethylphenoxy)-2-hydroxyplopyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine and its dihydrochloride, 45 m.p. 148-150°C, R^-1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,5-dimethylphenylaminocarbonylmethyl)piperazine and its dihydrochloride, m.p. 174°C, R,S-1-[3-(2-methoxyphenoxy)-2-hydroxyipropyl]-4-(4-methoxyphenylaminocarbonylmethyl)pii)erazine and its dihydrochloride, m.p. 162°C, R,S-1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(4-fluorophenylaminocarbonylmethyl)piperazine and its dihydrochloride, m.p. 169°C, R,S-1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(4-bromophenylaminocarbonylmethylpiperazine and its dihydrochloride, m.p. 170°C, R,S-1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethoxyphenylaminocarbonylmethyl)piperazine and its dihydrochloride, m.p. 155°C, R,S-1-i3-(2-methoxyphenoxy)-2-hydroxypropyl]- (4-)3,4-dimethoxyphenylaminocarbonylmethyl)- piperazine and its dihydrochloride, m.p. 132°C, ''*¦ R,S-l-[3^2-methoxyphenoxy)-2-h^142 760 29 4Hn-butylphenylaminocaribanylmethyl)pdperazine and its dihydrochloride, m.p. 180°C, R,S-1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4^2-methoxyphenyliamine kar^ and its dihydrochloride, m.p. 196°C, R,S-1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,4-dimethylphenylaminocarbonylmethyl)piperazine and its dihydrochloride, m.p. 202°C, R,S-1-[3-(2-isopyropoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine and its dihydrochloride, m.p. 180°C, R,S-1-[3-(2-n-butoxyphenoxy)-2-hydroxypropyl]-4-(2,5-dimethoxyphenylaminocarbonylmethyl)piperazine and its dihydrochloride, m.p. 160°C, R,S-1-[3-(methylphenylaminocarbonylmethyl)piperazine and its dihydrochloride, m.p. 154-156°C, R,S-1-[2-methoxyphenoxy)-2-hydroxypropyl]-4-(3-trifluoromethylphenylaminocarbonylmethyl)piperazine and its dihydrochloride, m.p. 158°C, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2-chloro-5H-methylphenylaminocarbonylmethyl)piperazine and its dihydrochloride, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(4-methylphenylaminocarbonylmethyl)piperazine and its hydrochloride, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(4-n-propylsulfinylphenylaminocarbonylmethyl)piperazine and its dihydrochloride, 1-[3-(2-chlorophenoxy)-2-hydroxypropyl)-4-(3,5-difluorophenylaminocarbonylmethyl)piperazine and its dihydrochloride, 1 -[3-(2-ethylphenoxy)-2-hydroxypropyl]-4-(phenylaminocarbonylmethyl)piperazine and its dihydrochloride, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethoxyphenylaminocarbonylmethyl)piperazine and its dihydrochloride, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(3-hydroxy-4-ethylphenylaminocarbonylmethyl)piperazine and its dihydrochloride, 1-[3-(4-methoxyphenoxy)-2-hydroxypropyl]-4-(phenylaminocarbonylmethyl)piperazine and its dihydrochloride, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2-cyanophenylaminocarbonylimethyl)piperazine and its dihydrochloride, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(4-acetamidophenylaminocarbonylmethyl)piperazine and its dihydrochloride, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(4-N-methylacetamidophenylaminocarboxymethyl)piperazine and its dihydrochloride, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(4-N-n-butylaminophenylaminocarbonylmethyl)piperazine and its dihydrochloride, 1-[3-(2-acetylphenoxy)-1-[3-(4-n-butyrylphenoxy)-2-hydroxypropyl]-4-(2,N-dimethylphenylaminocarbonylmethyl)piperazine and its dihydrochloride, 1-[3-(2-acetylphenoxy)-1-[3-(4-N,N-dimethylaminophenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine and its dihydrochloride, 1-[3-(2-acetylphenoxy)-1-[3-(4-N,N-dimethylaminophenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine and its dihydrochloride, 1-[3-(2-acetylphenoxy)-1-[3-(4-N,N-dimethylaminophenyl-2-hydroxypropyl]-4-(2,6-dimethylaminophenyl-2-hydroxypropyl]-4-(2,6-dimethylaminophenyl-2-hydroxypropyl]-4-(2,6-dimethylaminophenyl-2-hydroxypropyl)piperazine and its dihydrochloride, phenylamdnocarbonylnotyl)p(iperazine and its dihydrochloride, 1-[3-(5-n-butylphenoxy)-2-hydroxypropyl]-4-(phenylaminocarbonylmethyl)piiperazine and its dihydrochloride, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4- N-methyl-N-(2,6^ethoxyphenylaminocarbonyl-methyl)piperazine and its dihydrochloride, 1-(3-phenoxy-2-hydroxyEropyl)-4-(N-methyl-N-phenylaminocarbonyl-1-n^propyl)-piperazine and its dihydrochloride, i.e. 210°C, l-[3-(4-chlorophenoxy)-2-hydroxypropyl]-4- 1-(3-phenoxy-2-hydroxypropyl)-4-(N-methyl-N-phenylaminocarbonylmethyl-1-ethyl)piperazine and its dihydrochloride, m.p. 190°C, 1-(3-phenoxy-2-hydroxypropyl)-4-(N-methyl-N-phenylaminocarbonyl-1-ethyl)piperazine and its dihydrochloride, m.p. 168°C, 1-(3-phenoxy-2-hydroxypropyl)-4-(phenylaminocarbonylmethyl-1-ethyl)piperazine and its dihydrochloride, m.p. 148°C, 1-[3-(4-chlorophenoxy)-2-hydroxypropyl]-4-(N-methyl-N-phenylaminocarbonyl-1-ethyl)piperazine and its dihydrochloride, m.p. 210°C, 1-[3-(4-chlorophenoxy)-2-hydroxypropyl]-4-(N-methyl-N-phenylaminocarbonylmethyl-1-n-pentyl]piperazine and its dihydrochloride, m.p. 200°C, 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(4-methylthiophenylaminocarbonylmethyl)piperazine and its dihydrochloride, 1-(3-phenylthio-2-hydroxypropyl-4-)phenylaminocarbonylmethylpiperazine and its dihydrochloride, 1-[3-(4-methylphenylthio)-2-hydroxypropyl]-4-(phenylaminocarbonylmethyl)piperazine and its dihydrochloride, R,S-1-(3-phenylthio-2-hydroxypropyl)-4-(phenylaminocarbonyl-1-ethyl)piperazine hydrochloride and its dihydrochloride, R-S-1-(3-phenylthio-2-hydroxypropyl)-4-(N-phenyl-N-phenylaminocarbonylmethyl)piperazine and its dihydrochloride, mp 152°C. (b) By proceeding similarly to (a) above, but using a stoichiometrically equivalent amount of R- or S-1-phenoxy-2,3-epoxypropane instead of 1-(2-methylenedioxyphenoxy)-2,3-epoxypropane, the corresponding derivatives are obtained as salts of R or S configuration. (c) By proceeding similarly to (a) above, but using a stoichiometrically equivalent amount of R- or S-1-phenoxy-2,3-epoxypropane instead of 1-(2-methylenedioxyphenoxy)-2,3-epoxypropane, the corresponding derivatives are obtained as salts of R or S configuration. (a) above, but using a stoichiometrically equivalent amount of R- or S-1-(optionally substituted-phenylthio)-2,3-epoxypropane instead of R-1-(2-methoxyphenoxy)-2,3-epoxypropane, the corresponding derivatives are obtained as salts in the R or S orientation. Example 6. Salting of the free bases. 8 g of 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)-p-perazine are dissolved in methanol and acidified with methanolic hydrochloric acid. The precipitate is washed with ether to give 7.0 g of 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)-p-perazine dihydrochloride. [(2,6-dimethyloxypropyl)-4-(2,6-dimethylthanylmethyl)piperazine, m.p. 175-176°C. 10 15 20 25 30 35 40 45 50 55 6031 142 760 32 In a similar manner, all compounds of formula I in the form of free bases, prepared according to the process given in Example 4, may be converted into the corresponding pharmacologically acceptable acid addition salts. This is carried out by treatment with a suitable acid, for example hydrobromic, sulfuric, nitric, phosphoric, acetic, propionic, glycolic, provincial, oxalic, malonic, succinic, malic, maleic, funiric, tartaric, citric, benzoic, Example 7. Conversion of salt to free base. 10 g of 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbanylmethyl)piperazine dichloromethane was suspended in 50 ml of ether and stirred with an excess of dilute aqueous potassium carbonate solution until the salt was completely dissolved. The organic layer was separated, washed twice with water, dried over magnesium sulfate, and evaporated to give 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbanylmethyl)piperazine. in the form of the free salt. In a similar manner, the acid addition salts prepared by the method given in Example VI are converted to the corresponding free bases. Example VIII. Direct exchange of acid addition salts. 1 g of 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl]piperazine acetate is dissolved in 50 ml of 50% aqueous sulfuric acid solution and the solution is evaporated to dryness. The product is suspended in ethanol, filtered off, air-dried and crystallized from a mixture of methanol and acetone to give 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl]piperazine di(hydrogen sulfate). Example IX. Preparation of esters and dihydrochlorides of compounds of formula I. (a) 1 g of 1-{(3-H(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-methylphenylaminocarbonylmethyl)piperazine was dissolved in 25 ml of pyridine and cooled in an ice bath to 0-5°C. Then 0.6 g of acetic anhydride was slowly added and the reaction mixture was stirred for 2 hours. After adding 100 ml, the reaction mixture was extracted twice with 100 ml portions of ethyl ether. The combined extracts were washed twice with 100 ml of water and evaporated to dryness, giving 1-[3-(2-methoxyphenoxy)-2-acetoxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine as an oil. (b) By proceeding in a similar manner to (a) of this Example, but using a stoichiometrically equivalent amount of propionic anhydride, n-butyric anhydride, n-caproic anhydride, n-caprylic anhydride, or n-lauric anhydride in place of acetic anhydride, the following piperazines are prepared: 1-[3-(2-methoxyphenoxy)-2-propionyloxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine, 1-[3-(2-methoxyphenoxy)-2-butyryloxypropyl]- 1-(2,6-dimethylphenylaminocarbonylmethyl)piperazine, 1-[3-(2-methoxyphenoxy)-2-n-caproyloxypropyl]- 4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine, 1-[3-(2-methoxyphenoxy)-2-n-capryloyloxypropyl]- 4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine, 1-[3-(2-methoxyphenoxy)-2-n-capryloyloxypropyl]- 4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine. 1-[3-(2-methoxyphenoxy-2-n-lauroyloxypropyl]- 4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine. (c) Proceeding in a similar manner to (a) of this example, but using stoichiometry, an equivalent amount of alkanoic acid anhydride in place of acetic anhydride and using 1-[3-optionally substituted-phenoxy-2-hydroxypropyl]-4-(optionally substituted-phenylaminocarbonylmethyl)piperidine in place of 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine gives the corresponding 1-[optionally substituted-phenoxy-[alkanoyloxy-propyl]-4-(optionally substituted-phenylaminocarbonylmethyl)piperazine. (d) The compounds of (a), (b), or (c) of this Example are treated with excess hydrochloric acid as described in Example 8 to give the corresponding 1-[3-(optionally substituted-phenoxy)-2-alkanoyloxypropyl]-4-(optionally substituted-phenylaminocarbonylmethyl)piperazine dichloride. In all of the reactions described in (a), (b), (c), and (d) of this Example, the phenoxy compounds are to be replaced by optionally substituted thiophenoxy compounds, the stereochemistry of the compounds of formula I remaining unchanged. Example X. A solution of 3.5 g of 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine dihydrochloride in 50 ml of water was adjusted to pH 12 with ammonium hydroxide solution and extracted with methylene chloride. The methylene chloride was evaporated, yielding 3 g of 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine as the free base. In a similar manner, the acid addition salts prepared by the procedures given in Examples 6 and 8 were converted to the corresponding free base. 55 Patent Claims 1. A method for preparing new piperazine derivatives of the general formula 1, wherein R1, Rf, R*, R4 and R5 are the same or different and represent a hydrogen atom, a lower alkyl group, a lower alkoxy group, a cyano group, a trifluoromethyl group, a halogen atom, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkylsulfonyl group or an alkamido group optionally substituted on the nitrogen atom, or Rf and Rf together form a —OCH*O— group, R6, R7, R8, R9 and R1§ are the same or different and represent a hydrogen atom, a lower acyl group, an aminocarbinoylmethyl group, and a an aryl group, a cyano group, a lower alkyl group, a lower alkoxy group, a trifluoromethyl group, a halogen atom, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkylsulfonyl group or a lower dialkylamino group, or R6 and R7 together form the group —CH=CH—CH=CH—, or R7 and R8 together form the group —OCHfO—, R11 and R12 are the same or different and represent a hydrogen atom or a lower alkyl group, and W represents an oxygen or sulfur atom, and when R1 represents a methyl group, then R4 has a meaning other than a methyl group, and pharmacologically acceptable esters and acid addition salts of these compounds, characterized in that the compound of the general formula 4, in which R8, R7, R8, R9, R10 and W are as defined above, are reacted with a compound of general formula V, wherein X is a leaving group and R1, R1, R11, R12, R4, R5, R11 and IR" are as defined above, whereupon the compound of formula I in salt form is converted into the free base, or the compound of formula I in free base form is converted into a pharmacologically acceptable acid addition salt, or the salt of the compound of formula I is converted into another pharmacologically acceptable salt of the compound of formula I, or the compound of formula I or a salt thereof is converted into a pharmacologically acceptable ester, or the compound of formula I or a salt or ester thereof is separated into stereoisomers. 2. Process 2. The method according to claim 1, wherein for the preparation of 1-(3-phenoxy-2-hydroxypropyl-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine and its pharmacologically acceptable acid addition salts, 1-(3-phenoxy-2-hydroxypropyl)piperazine is reacted with 2,6-dimethylphenylaminocarbonylmethyl chloride. 3. The method according to claim 1, wherein for the preparation of 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl)piperazine and its pharmacologically acceptable acid addition salts, 1-[3- (2-Methoxyphenoxy)-2-hydroxypropyl]piperazine is reacted with 2,6-dimethylphenylaminocarbonylmethyl chloride. 4. A process according to claim 3, characterized in that in the case of preparing R-1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethylpiperazine and its pharmacologically acceptable acid addition salts, R-1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]piperazine is reacted with 2,6-dimethylphenylaminocarbonylmethyl chloride. 5. A process according to claim 3, characterized in that in the case of preparing S-1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethylpiperazine and its pharmacologically acceptable acid addition salts, [3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-(2,6-dimethylphenylaminocarbonylmethyl]piperazine and its pharmacologically acceptable acid addition salts, S-1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]piperazine is reacted with 2,6-dimethylphenylaminocarbonylmethyl chloride. Active substance I * H HI IV Table 2 Specific cytotoxicity (%) < 0.02 3 23 Active substance in 0.2 ml PBS [µg culture 0.2 39 21 81 18 2 59 48 47 20 20 74 I Active substance in 100 [xg liposomes | per 0.2 ml [µg culture 0.02 64 64 0.2 56 10 76 68 2 51 23 79 52 20 44 11142 760 R' R" OH RH R< R2 ^-^-W-CHrC-CH^-O-CH-C-N —H-R R* R6 H r« Ó ds d4 RiZ 0 Formula 1 R5 R4 H r*t Formula 2 H •*N f H CH3 H 0-CH2-^-CH2-nCn-CH2- C - N -4j&- H H' DCH3 H 6 c£\ R* R<° OH R8-^W-CHfC-CH2-rQlH R6 R H R" R< R2 X-CH-C-N -^-R8 R<2 0 R5 R4 R9v ,,R10 Wiar 7142 760 Ar-W-H+ CI-CH2-CH-CH2 W7ArR I XnX mór 9 Ar1-W-CH2-CH -CH2 + HlfilH Pattern ; Formula HOH | Ar1-W-CH2-C- CHZ- nQJH + u " 0 R11 X-CH-CCl + H-N^\r2 R<2 mór iZ } 0 R" M^a/- ye PL PL PL PL PL PL PL PL PL

Claims (1)

1.